HUT50440A - Process for producing pharmaceutical compositions for treating schizophrenia - Google Patents

Description

FIELD OF THE INVENTION The present invention relates to the manufacture of a medicament for the treatment of schizophrenia, in particular deficient forms thereof, comprising 2-amino-6- (trifluoromethoxy) benzothiazole or a pharmaceutically acceptable salt thereof.

No. 50,551. It is known from European Patent Application 2-amino-6- (trifluoromethoxy) benzothiazole that is an anticonvulsant, anxiolytic and hypnotic drug.

We have found that 2-amino-6- (trifluoromethoxy) benzothiazole or a pharmaceutically acceptable salt thereof is effective in treating schizophrenia, particularly its deficient forms.

New therapeutic applications of the compound in humans have been investigated, treating patients with this single compound alone. Twenty-six patients with schizophrenia were treated orally for 15 days with a daily dose of 15θ mg.

The efficacy of the compound was determined by the following series of evaluations:

- SANS, Andreasen Deficient Symptom Evaluation Series CAndreasen, N.C., Aroh · Gene. Peychiatry, 39 · k. 784-788 (1982)];

BPRS Brief Psychiatric Rating Scale, (short psychiatric evaluation series) (Pichot, P. et al., Revue de Psychologie Appliquée, 19, 19, No. 217-232, 1969).

Ilamilton's anxiety assay series [Beck, P., et al., Acta Psychiatrica Scandinavica, No. 326]. 73 · k. Ρ · 9 ·, 19–22. (1986)];

······································· (CGCGC Global Clinical Impression, ECDEU assessment manual, published by United States of America. Ministry of Health, Education and Welfare, p. 218-2211 ·

The most important symptoms that have improved are:

- re-establishing contact with the outside world,

- the patient is more active in both physical and mental aspects,

- resocialisation,

- improvement in sleep.

No clinical side effects were observed.

2-Amino-6- (trifluoromethoxy) benzothiazole is disclosed in U.S. Pat. can be prepared according to the process described in European Patent Application 4,284,500.

Pharmaceutical compositions for the treatment of schizophrenia either contain only 2-amino-6- (trifluoromethoxy) benzothiazole or a pharmaceutically acceptable salt thereof, or it is contained in combination with other pharmaceutically compatible, inhaled or physiologically active substances. The pharmaceutical compositions may be administered orally, perorally, or rectally.

Solid oral dosage forms include tablets, pills, powders (gelatine capsules, wafers) or granules. In these pharmaceutical compositions, the active ingredient is mixed with one or more inert diluents, such as starch, cellulose, sugar, lactose or silica. The formulations may contain, in addition to diluents, one or more lubricants such as magnesium stearate or talc, a coloring agent, a coating (dragee) or a varnish.

Liquid oral pharmaceutical formulations include solutions, suspensions, emulsions, syrups, elixirs containing an inert diluent such as water, ethanol, glycerol, vegetable oils, or paraffin oil. In addition to diluents, the compositions may contain, for example, a wetting agent, a sweetening agent, a shampooing agent, a muscle repair agent or a stabilizer.

Sterile parenteral formulations are preferably non-aqueous solutions, suspensions or emulsions. As a solvent or vehicle, water, propylene glycol, polyethylene glycol, vegetable oils, especially olive oil, or its injectable organic ester, such as ethyl oleate or other suitable organic solvent, may be used. These formulations may contain other excipients, in particular wetting agents, isotonizing agents, emulsifying agents, dispersing agents and stabilizing agents. Sterilization may be accomplished in various ways, by aseptic filtration, by incorporation of the sterilizing agent, by irradiation or by heat. It can also be prepared in the form of solid, sterile formulations and dissolved in sterile, sterile forms immediately prior to use, · · · · · · · · · · · · · · · · · · · · · · ·· ··

- in 5 disposable media ·

Suppositories are suppositories or rectal capsules which contain, in addition to the active ingredient, carriers such as cocoa butter, semi-synthetic glycerides or polyethylene glycol.

The dose will depend on the type of disease, the duration of treatment and the form of the medicine used; it is usually from 10 mg to 200 mg per day in single doses ranging from 2 mg to 50 mg for oral administration to adults.

Generally, the dosage will be determined by the physician, depending on the age, weight and other characteristics of the patient being treated.

The following examples illustrate the preparation of pharmaceutical compositions for treating schizophrenia:

The example

The usual method is to prepare a gelatin capsule containing 50 mg of the active ingredient and having the following composition:

2-amino-O- (trifluoromethoxy) benzothiazole 50 mg cellulose 18 mg lactose 55 mg colloidal diatomaceous earth 1 mg carboxymethyl starch sodium 10 mg

Conventionally, 50 mg of the active ingredient is contained in talc · mmgné zixnn- a z tearate

Example B mg mg milligram tablets are prepared having the following composition:

2-amino-6- (trifluoro-methoxy) benzothiazol 50 mg milk sugar 104 mg oellulóz 40 mg poly (vinyl pyrrolidone) 10 mg arm boxi-ine ti-l 1 hard sodium 22 mg saucer 10 mg magnózium stearate 2 mg colloidal diatomaceous earth 2 mg

a mixture of hydroxymethylcellulose, glycerol and tltane-dloxld 72: 3.5: 24.5 q.s. 1 tablet to make 245 mg with coating ·

Example C A solution for injection containing mg of the active ingredient is prepared having the following composition:

2-amino-6- (trifluoromethoxy) -benzotiazo1 10 mg benzoic acid 80 mg

0.06 ml benzyl alcohol sodium benzoate% ethanol sodium hydroxide propylene glycol water mg

0.4 ml mg

1.6 ml

qs For 4 ml

V

Claims (1)

Procedure as 2-amino-6- (trifluoromethoxy) as an active ingredient for the preparation of pharmaceutical compositions containing benzothiazole or pharmaceutically acceptable salts thereof, characterized in that 2-amino-6- (trifluoromethoxy) benzothiazole or a pharmaceutically acceptable salt thereof is prepared in a manner known per se for the treatment of schizophrenia and in particular deficient forms thereof.